The prostaglandins are a class of humoral agents implicated in the regulation of virtually all mammalian cell types and organs. A one-year continuation of support for studies of the mechanism of action of prostanoids in biological systems related to their in vivo actions in man is proposed. The particular goals and methods proposed are: 1) studies of transport requirements for prostacyclin (PI), prostaglandin (PG), and thromboxane (TXA2) actions in blood constituents and other elements of the cardiovascular system; 2) biomimetic syntheses of prostacyclins; 3) studies of TXA2 and PI mimics in vivo in the baboon: 4) an attempt at a total synthesis of a chemically stable TXA2 isostere; and 5) structure-activity correlations for PI diastereomers and analogs displaying agonistic (rather than antagonistic) actions on either the blood platelet or the vasculature. The method to be employed towards goals 1) (and to some extent goal 3)) is the synthesis of fully characterized polymer tethered versions of PGE1, other PI mimics, and TXA2 mimics. Initial studies will use human serum albumin and agarose as the polymer anchors. The tethered-analogs will be used to determine the locations of TXA2, PI, and PG receptors on the platelet and in other parts of the cardiovascular system.